Preeclampsia is a complication in up to 8% of pregnancies and accounts for significant perinatal morbidity and mortality (1, 2). No definitive etiology or specific predictors of the disease has been identified to date. Furthermore, there has been little progress in the treatment of this disorder; the cure remains delivery of the fetus and removal of the placenta.
As early as 1915, Williams hypothesized the presence of toxic factors in the blood of women with the clinical syndrome of “toxemia” or preeclampsia (25). A number of subsequent studies, aimed at determining whether blood from pregnant women or placental extracts contained factors responsible for hypertension, yielded contradictory results (26-28). Tatum and Mule reported that whole blood collected from patients with severe preeclampsia could induce transient hypertension when transfused to the same patient in the post partum period (28). Pirani and Macgillivray reported similar observations after injecting plasma from eclamptic women 6 days after delivery (29). Since the increase in blood pressure could not be elicited by re-transfusion 6 weeks postpartum, the authors concluded that patients with preeclampsia had increased sensitivity to pressor agent(s) lasting about 1 week after delivery, but not as long as 6 weeks. Thereafter, considerable effort was devoted to the identification of the pressor agent responsible for this effect in the maternal circulation. Over the years, the focus has encompassed the renin-angiotensin system (30, 31), norepinephrine (32, 33), vasopressin (34), prostaglandins (35), endothelin (36) and others (37, 38). Despite all efforts, the factor(s) responsible for these effects remains to be elucidated.
The hallmark of normal placentation is the invasion of trophoblast cells into the decidual and myometrial segments of the spiral arteries, resulting in the reversible obliteration of the normal arterial wall architecture (3). Muscular, medial elastic, and endothelial layers of the arteriolar walls are invaded by trophoblasts and replaced by fibrinoid material, converting narrow-lumen spiral arteries into large-bore utero-placental vessels (4). In contrast, failure of physiologic transformation of the myometrial segment of the spiral arteries is characteristic of abnormal placentation and has been considered central to the pathophysiology of preeclampsia for the past 30 years (5, 3, 6). Moreover, recent microscopic studies of placental specimens from women with preeclampsia have demonstrated that the extra villous trophoblasts anchoring the placenta to the uterine wall show marked apoptosis as early as the first trimester (7, 8), suggesting that the initial insult occurs early in gestation and may involve the trophoblast (9, 10, 11).
Around the second postconceptional week, the cytotrophoblast and syncytiotrophoblast differentiate from the implanted blastocyst (47). The cytotrophoblast divides to form syncytiotrophoblasts and further proliferates to form a specialized trophoblast referred to as an extravillous trophoblast. It is the extravillous trophoblast that extends through the endometrium to reach the border of the decidua and myometrium. The extravillous trophoblast continues its invasion into the spiral arterioles and replaces the endothelial and muscular linings of the uterine arterioles, leading to vasodilation of the uterine vasculature (7). This change ensures a continued low resistance system, which potentiates maternal blood flow to the intervillous space and maintains adequate perfusion of the developing fetus.
In preeclampsia, with the absence of marked vasodilation and with the lumen of the vessels essentially occluded, blood flow and oxygen transfer to the fetus is diminished, leading to the maternal manifestations of preeclampsia as well as the fetal manifestations of oligohydramnios and intrauterine growth restriction (IUGR). One theory to explain the etiology of preeclampsia implicates an injured placenta leading to hypoperfusion of the implantation site and endothelial cell damage (48).
It would be useful to be able to identify patients at risk of developing preeclampsia.